The program is a continuation of the study on the neurophysiology of the enteric nervous system and of the investigation of the mechanisms by which the intrinsic nervous system of the gut participates in the control and integration of gastrointestinal function. The objectives of the study are: (1) To compare the electrical behavior of enteric neurons with the behavior of the effector systems in the specialized regions along the alimentary canal. (2) To map the interneuronal connectivity that mediates the various reflex responses that occur within the gut. (3) To determine the effects of pharmacological agents, ischemia and intrinsic humoral factors circulating in the blood on electrical behavior of enteric neurons. (4) To determine if the internal environment of enteric ganglia is regulated by a selectively permeable barrier. (5) To determine the metabolic properties of the enteric nervous system and to obtain an explanation for the low susceptibility of enteric neurons to hypoxia. (6) To compare effector function in the large intestine of mice with herditary aganglionic megacolon with effector function in mice with normal innervation of the bowel. (7) To elucidate the etiology and pathophysiology of Hirschsprung's disease and related disorders that are associated with malformation and malfunction of the enteric nervous system.